Lethal and sublethal impacts of membrane-fed ivermectin are concentration dependent in Anopheles coluzzii.

Abstract

Ivermectin is a well-tolerated anthelminthic drug with wide clinical and veterinary applications. It also has lethal and sublethal effects on mosquitoes. Mass drug administration with ivermectin has therefore been suggested as an innovative vector control tool in efforts to curb emerging insecticide resistance and reduce residual malaria transition. To support assessments of the feasibility and efficacy of current and future formulations of ivermectin for vector control, we sought to establish the relationship between ivermectin concentration and its lethal and sublethal impacts in a primary malaria vector. The in vitro effects of ivermectin on daily mortality and fecundity, measured by egg production, were assessed up to 14 days post-blood feed in a laboratory colony of Anopheles coluzzii. Mosquitoes were fed ivermectin in blood meals delivered by membrane feeding at one of six concentrations: 0ng/ml (control), 10ng/ml, 15ng/ml, 25ng/ml, 50ng/ml, 75ng/ml, and 100ng/ml. Ivermectin had a significant effect on mosquito survival in a concentration-dependent manner. The LC50 at 7days was 19.7ng/ml. The time to median mortality at ≥ 50ng/ml was ≤ 4days, compared to 9.6days for control, and 6.3-7.6days for ivermectin concentrations between 10 and 25ng/ml. Fecundity was also affected; no oviposition was observed in surviving females from the two highest concentration treatment groups. While females exposed to 10 to 50ng/ml of ivermectin did oviposit, significantly fewer did so in the 50ng/ml treatment group compared to the control, and they also produced significantly fewer eggs. Our results showed ivermectin reduced mosquito survival in a concentration-dependent manner and at ≥ 50ng/ml significantly reduced fecundity in An. coluzzii. Results indicate that levels of ivermectin found in human blood following ingestion of a single 150-200μg/kg dose would be sufficient to achieve 50% mortality across 7days; however, fecundity in survivors is unlikely to be affected. At higher doses, a substantial impact on both survival and fecundity is likely. Treating human populations with ivermectin could be used as a supplementary malaria vector control method to kill mosquito populations and supress their reproduction; however strategies to safely maintain mosquitocidal blood levels of ivermectin against all Anopheles species require development.